Bacteria-related infection represents the most significant hurdle to normal wound healing resulting in >100,000 deaths in the United States each year. Due to the emergence of antibiotic resistant bacteria and the concomitant decrease in effective drug (i.e., antibiotic) development against such strains, the threat of life-threatening infections is ever increasing. Several small biotechnology companies are working towards the development of new, cost-effective wound treatments with widespread antibacterial efficacy. Unfortunately, many current approaches are complex, cost prohibitive, and only mildly effective against the most severe bacteria strains. Nitric oxide (NO) has garnered much attention as a therapeutic because of its role in blood pressure regulation (e.g., vasodilation), wound healing, and the immune response, particularly against bacteria. Current scientific knowledge regarding NO's role in immune system response and its proven antibacterial activity suggest that therapies based on NO release may represent a new paradigm for treating skin wounds. Novan, Inc. (Nitric Oxide Vehicles and Nanotechnology) was established in January 2006 to commercialize chemical strategies that safely and controllably deliver therapeutic concentrations of NO. The primary aim of this Phase I STTR proposal is to develop an antibacterial wound dressing based on NO-releasing silica nanoparticles that delivers effective concentrations of NO to the site of a wound. Our specific objectives include: 1) developing a topical formulation capable of controllably releasing NO at appropriate levels to treat infection and serve as a barrier to further colonization of an external wound site;and, 2) evaluating the broad-spectrum antibacterial activity of the NO-releasing nanoparticles against an extended set of gram negative and gram-positive bacteria. The nanoparticle synthesis and antibacterial testing will be a joint effort between Novan, Inc. and its partnering institution, the University of North Carolina at Chapel Hill. Cirrus Pharmaceuticals, Inc., a contract research organization in Durham, NC, will assist in the development of a polymeric wound dressing formulation to accommodate the nanoparticles. Both NO release stability and activity will be evaluated as a function of polymer composition. The goal in Phase I am to develop a NO-releasing wound barrier dressing with proven bactericidal activity.